Ambulatory blood pressure response to triple therapy with an angiotensin-receptor blocker (ARB), calcium-channel blocker (CCB), and HCTZ versus dual therapy with an ARB and HCTZ

Daniel Duprez¹, Keith Ferdinand², Das Purkayastha³, Rita Samuel³, Richard Wright^4
1University of Minnesota, Minneapolis, MN, ²Atlanta Clinical Research Centers, Atlanta, GA, ³Novartis Pharmaceuticals Corporation, East Hanover, NJ, ⁴Pacific Heart Institute, Santa Monica, CA, USA

Background: Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) is a useful tool for assessing antihypertensive drugs and their combinations.
Objective: To compare the effect of a moderate dose of angiotensin receptor blocker/calcium channel blocker (ARB/CCB) combined with a diuretic versus a maximal dose of ARB with a diuretic on 24-hour ambulatory blood pressure monitoring (ABPM) and other derived ambulatory blood pressure (ABP) parameters.
Methods: The EXforge As compared to Losartan Treatment ABPM substudy was a randomized, double-blind, parallel-group, active-control, forced-titration study of patients with Stage 2 hypertension that compared the efficacy of initial treatment with valsartan/amlodipine 160/5 mg (n = 48) or losartan 100 mg (n = 36). At week 3, hydrochlorothiazide (HCTZ) 25 mg was added in both treatment groups. ABP was measured at baseline and at week 6. Additionaly, 24-hour ABP, nighttime (10 pm to 6 am) and daytime (6 am to 10 pm) ABP, and ABP load (percentage of readings above 140/90 mmHg) were determined.
Results: Eighty-four patients (48 ARB/CCB/HCTZ, 36 ARB/HCTZ) had ABPM at baseline and at week 6. Reductions of systolic/diastolic ABP were greater in the ARB/CCB/HCTZ group than in the ARB/HCTZ group for 24-hour mean ABP (–22.0/–13.3 versus –17.4/–8.1 mmHg), as well as nighttime ABP (–22.2/–13.3 versus –16.2/–7.4 mmHg), daytime ABP (–21.9/–13.0 versus –18.1/–8.6 mmHg), ABP in the last 4 hours of the dosing period (–21.5/–13.5 versus –17.0/–7.7 mmHg), and ABP load (21.7%/12.8% versus 30.8%/20.0%).
Conclusion: Initiating antihypertensive treatment with moderate doses of ARB/CCB with a diuretic is more effective in lowering nighttime and daytime ABP and reducing ABP load than a maximal dose of an ARB with a diuretic.

Keywords: antihypertensive drugs, ambulatory blood pressure, ambulatory blood pressure monitoring, combination therapy, valsartan, amlodipine, hydrochlorothiazide, losartan